화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.526, No.3, 728-732, 2020
Dimeric dihydrodiol dehydrogenase is an efficient primate 1,5-anhydro-D-fructose reductase
1,5-Anhydro-D-fructose (AF), a metabolite of the anhydrofructose pathway of glycogen metabolism, has recently been shown to react with intracellular proteins and form advanced glycation end-products. The reactive AF is metabolized to non-reactive 1,5-anhydro-D-glucitol by AF reductase in animal tissues and human cells. Pig and mouse AF reductases were characterized, but primate AF reductase remains unknown. Here, we examined the AF-reducing activity of eleven primate NADPH-dependent reductases with broad substrate specificity for carbonyl compounds. AF was reduced by monkey dimeric dihydrodiol dehydrogenase (DHDH), human aldehyde reductase (AKR1A1) and human dicarbonyl/L-xylulose reductase (DCXR). DHDH showed the lowest K-M (21 mu M) for AF, and its k(cat)/K-M value (1208 s(-1) mM(-1)) was much higher than those of AKR1A1 (1.3 s(-1) mM(-1)), DCXR (1.1 s(-1) mM(-1)) and the pig and mouse AF reductases. AF is a novel substrate with higher affinity and catalytic efficiency than known substrates of DHDH. Docking simulation study suggested that Lys156 in the substrate-binding site of DHDH contributes to the high affinity for AF. Gene database searches identified DHDH homologues (with >95% amino acid sequence identity) in humans and apes. Thus, DHDH acts as an efficient AF reductase in primates. (C) 2020 Elsevier Inc. All rights reserved.